title: Novel multifunctional chitosan-GMA-IDA-Cu(II) nanospheres for high dynamic range characterization of the human plasma proteome.
abstract: In this study, we describe characterization of the human plasma proteome based on analysis with multifunctional chitosan-GMA-IDA-Cu(II) nanospheres. Chitosan-GMA-IDA-Cu(II) nanospheres with diameters of 20 to 100 nm have unique properties due to multifunctional chemical moieties, high surface area, high capacity, good dispersibility in buffer solution as well as good biocompatibility and chemical stability which improves their specific interaction with peptides and proteins of the human plasma using different binding buffers. Combining these chitosan-GMA-IDA-Cu(II) nanospheres with MS spectrometry results in a novel strategy which should make it possible to characterize the plasma proteome in a single test. Peptides and proteins adsorbed on the nanosphere can be directly detected by MALDI-TOF-MS. The eluted lower molecular weight peptides and proteins are identified by nano-LC-ESI-MS/MS. A total of 842 unique LMW peptides and 1,682 human unredundant proteins IDs were identified in two different binding buffers, which included relatively low-level proteins (e.g., pg/mL of IL3 Interleukin-3) co-distributed with high-abundance proteins (e.g., 35-55 mg/mL level serum albumin). As such, this nanosphere technique selectively enabled the identification of proteins over a dynamic range of greater than 8 orders of magnitude. Considering this capacity for selective enrichment of peptides and proteins in human plasma, and the large number of LMW peptides and proteins which can be identified, this method promises to accelerate discovery of biomarkers for clinical application.
authors.affiliation: Proteomics Laboratory, Medical and Healthy Analytical Center, Peking University, Beijing, China. zouxj@bjmu.edu.cn
authors.forename: Xiajuan
authors.initials: X
authors.lastname: Zou
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhong
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lou
authors.forename: Jiarou
authors.initials: J
authors.lastname: Peng
authors.forename: Matthias
authors.initials: M
authors.lastname: Rainer
authors.forename: Isabel
authors.initials: I
authors.lastname: Feuerstein
authors.forename: Najam-ul-Haq
authors.initials: NU
authors.lastname: Muhammad
authors.forename: Christian W
authors.initials: CW
authors.lastname: Huck
authors.forename: Günther K
authors.initials: GK
authors.lastname: Bonn
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
mesh_terms: D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007098:Imino Acids / Q000737:chemistry* / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry* / Q000378:metabolism; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D020543:Proteome / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
chemical_list: D004852:Epoxy Compounds; D007098:Imino Acids; D008689:Methacrylates; D020543:Proteome; C030699:copper(II)-iminodiacetate; D048271:Chitosan; C007870:glycidyl methacrylate